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Desire Collen - One of the best experts on this subject based on the ideXlab platform.
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comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of Streptokinase and recombinant staphylokinase in baboons
Circulation, 1993Co-Authors: Desire Collen, F De Cock, J M StassenAbstract:BACKGROUND Streptokinase is a routinely used thrombolytic agent that is immunogenic and relatively inefficient toward platelet-rich thrombus, whereas staphylokinase is a poorly studied fibrinolytic agent. Here, the comparative immunogenicity and thrombolytic properties toward arterial platelet-rich thrombus and venous whole blood clots of Streptokinase and recombinant staphylokinase were studied in baboons. METHODS AND RESULTS The inhibitory capacity of baboon plasma (in a human plasma-based clot lysis assay) was 0.39 +/- 0.25 microgram Streptokinase and 0.04 +/- 0.05 microgram recombinant staphylokinase per milliliter of plasma (mean +/- SD, n = 9). Intravenous infusion over 1 hour of 0.300 mg/kg of Streptokinase at 0, 1, 2, 3, and 5 weeks in five baboons given heparin and the antiplatelet agent ridogrel increased the Streptokinase-neutralizing titer from 0.22 +/- 0.18 microgram/mL plasma at baseline to 3.8 +/- 4.4 micrograms/mL after 2 weeks (p = 0.043 versus baseline by Wilcoxon signed rank test) and to 4.4 +/- 4.6 micrograms/mL after 5 weeks, whereas the thrombolytic potency toward a 125I-fibrin-labeled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 84 +/- 7% at baseline to 45 +/- 8% after 2 weeks and to 36 +/- 8% after 5 weeks (p 50%) decrease in blood pressure, requiring administration of steroids and intravenous fluids, and a marked increase in leukocyte count and hemoglobin concentration. Intravenous infusion of Streptokinase or recombinant staphylokinase over 1 hour in doses ranging between 0 and 1.0 mg/kg in three groups of four baboons each induced dose-dependent lysis of a 125I-fibrin-labeled autologous jugular vein blood clot (50% lysis requiring 0.140 mg/kg Streptokinase and 0.058 mg/kg recombinant staphylokinase, representing equimolar amounts of 3.25 nmol/kg) without systemic fibrinogen depletion. The thrombolytic potency toward platelet-rich arterial thrombus of Streptokinase and recombinant staphylokinase were studied in a femoral arterial eversion graft model. Arterial recanalization with recombinant staphylokinase was more frequent and more persistent than with Streptokinase (all p CONCLUSIONS Recombinant staphylokinase has a thrombolytic potency toward jugular vein blood clots in baboons comparable to that of Streptokinase, but it is less immunogenic and less allergenic and it does not induce resistance to lysis upon repeated administration; it is significantly more efficient than Streptokinase for the dissolution of platelet-rich arterial eversion graft thrombi. Recombinant staphylokinase, which can be easily obtained in active form by expression in Escherichia coli, may constitute a potentially useful alternative to Streptokinase for the treatment of acute myocardial infarction.
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comparative thrombolytic and immunogenic properties of staphylokinase and Streptokinase
Fibrinolysis and Proteolysis, 1992Co-Authors: Desire Collen, I Vanlinthout, F De Cock, H. Roger Lijnen, Paul Declerck, J M StassenAbstract:The comparative thrombolytic properties of natural (STAN) and recombinant (STAR) staphylokinase (STA) and of Streptokinase were studied in hamsters with a pulmonary embolus consisting of a platelet-poor, platelet-rich (300000 platelets/μI), platelet-enriched (1500 000 platelets/ μl) or mechanically compressed human plasma clot. Intravenous infusion over 1 h in doses ranging between 0 and 0.50 mg/kg induced dose-dependent progressive clot lysis without systemic fibrinogen breakdown. The relative thrombolytic potencies, on a weight base, of the STA preparations versus Streptokinase were comparable in the platelet-poor clot model (50% lysis requiring 13 μg/kg STA and 12 μg/kg Streptokinase) and in the platelet-rich clot model (50% lysis with 28 μg/kg STA and with 32 μg/kg Streptokinase), but 5-fold higher in the platelet-enriched clot model (50% lysis with 46 μg/kg STA and with 210 μ/kg Streptokinase) and 2-fold higher in the mechanically compressed clot model (50% lysis with 36 μg/kg STA and with 71 μg/kg Streptokinase). Dog plasma at baseline contained Streptokinase-neutralising activity (neutralising 0.24±0.14 μg Streptokinase per ml plasma in a human plasma-based clot lysis assay, mean ±SD) but apparently no STA-neutralising activity. Repeated administration of 40 μg/kg over 1 h of Streptokinase at weekly intervals in 5 dogs, increased the Streptokinase-neutralising titre to 1.1±0.98 μg/ml plasma after 2 weeks and to 2.9±2.5 μg/ml after 3 weeks (p=0.13 and 0.05 versus baseline, respectively), whereas the thrombolytic potency towards a 125I-fibrin-labelled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 58±4% at baseline to 10±3% after 2 weeks and 4±1% after 3 weeks (p<0.001 vs baseline). Repeated weekly administration of an equipotent dose of STA (4 μg/kg) did not induce measurable STA-neutralising activity after 2 weeks and was associated with persistent, although somewhat reduced clot lysis (58 ± 4% lysis at baseline and 33±7% at 2 weeks, p=0.02). After 3 weeks however, STA-neutralising activity became detectable in plasma (0.34±0.30 μg/ml, p=0.07 vs baseline) and resistance to clot lysis became obvious (6±2% versus a baseline value of 58±4%, p<0.01). Thus, in the hamster model, STA has a thrombolytic potency towards platelet-poor and platelet-rich clots comparable to that of Streptokinase, but it is relatively more efficient than Streptokinase for the dissolution of platelet-enriched or retracted clots. Furthermore, STA might be less immunogenic than Streptokinase as evidenced by less rapid induction of antibody formation and resistance to clot lysis upon repeated administration. Thrombolytic therapy of patients with acute myocardial infarction with STA thus might constitute a potential alternative to treatment with Streptokinase, with a better efficacy towards platelet-rich arterial clots and possibly with reduced allergic side effects.
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comparative fibrinolytic properties of staphylokinase and Streptokinase in animal models of venous thrombosis
Thrombosis and Haemostasis, 1991Co-Authors: H. Roger Lijnen, J M Stassen, Kiyotaka Okada, Hideharu Fukao, Osamu Matsuo, I Vanlinthout, Desire CollenAbstract:: The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of Streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and Streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, Streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg Streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than Streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than Streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for Streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for Streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
J M Stassen - One of the best experts on this subject based on the ideXlab platform.
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comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of Streptokinase and recombinant staphylokinase in baboons
Circulation, 1993Co-Authors: Desire Collen, F De Cock, J M StassenAbstract:BACKGROUND Streptokinase is a routinely used thrombolytic agent that is immunogenic and relatively inefficient toward platelet-rich thrombus, whereas staphylokinase is a poorly studied fibrinolytic agent. Here, the comparative immunogenicity and thrombolytic properties toward arterial platelet-rich thrombus and venous whole blood clots of Streptokinase and recombinant staphylokinase were studied in baboons. METHODS AND RESULTS The inhibitory capacity of baboon plasma (in a human plasma-based clot lysis assay) was 0.39 +/- 0.25 microgram Streptokinase and 0.04 +/- 0.05 microgram recombinant staphylokinase per milliliter of plasma (mean +/- SD, n = 9). Intravenous infusion over 1 hour of 0.300 mg/kg of Streptokinase at 0, 1, 2, 3, and 5 weeks in five baboons given heparin and the antiplatelet agent ridogrel increased the Streptokinase-neutralizing titer from 0.22 +/- 0.18 microgram/mL plasma at baseline to 3.8 +/- 4.4 micrograms/mL after 2 weeks (p = 0.043 versus baseline by Wilcoxon signed rank test) and to 4.4 +/- 4.6 micrograms/mL after 5 weeks, whereas the thrombolytic potency toward a 125I-fibrin-labeled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 84 +/- 7% at baseline to 45 +/- 8% after 2 weeks and to 36 +/- 8% after 5 weeks (p 50%) decrease in blood pressure, requiring administration of steroids and intravenous fluids, and a marked increase in leukocyte count and hemoglobin concentration. Intravenous infusion of Streptokinase or recombinant staphylokinase over 1 hour in doses ranging between 0 and 1.0 mg/kg in three groups of four baboons each induced dose-dependent lysis of a 125I-fibrin-labeled autologous jugular vein blood clot (50% lysis requiring 0.140 mg/kg Streptokinase and 0.058 mg/kg recombinant staphylokinase, representing equimolar amounts of 3.25 nmol/kg) without systemic fibrinogen depletion. The thrombolytic potency toward platelet-rich arterial thrombus of Streptokinase and recombinant staphylokinase were studied in a femoral arterial eversion graft model. Arterial recanalization with recombinant staphylokinase was more frequent and more persistent than with Streptokinase (all p CONCLUSIONS Recombinant staphylokinase has a thrombolytic potency toward jugular vein blood clots in baboons comparable to that of Streptokinase, but it is less immunogenic and less allergenic and it does not induce resistance to lysis upon repeated administration; it is significantly more efficient than Streptokinase for the dissolution of platelet-rich arterial eversion graft thrombi. Recombinant staphylokinase, which can be easily obtained in active form by expression in Escherichia coli, may constitute a potentially useful alternative to Streptokinase for the treatment of acute myocardial infarction.
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comparative thrombolytic and immunogenic properties of staphylokinase and Streptokinase
Fibrinolysis and Proteolysis, 1992Co-Authors: Desire Collen, I Vanlinthout, F De Cock, H. Roger Lijnen, Paul Declerck, J M StassenAbstract:The comparative thrombolytic properties of natural (STAN) and recombinant (STAR) staphylokinase (STA) and of Streptokinase were studied in hamsters with a pulmonary embolus consisting of a platelet-poor, platelet-rich (300000 platelets/μI), platelet-enriched (1500 000 platelets/ μl) or mechanically compressed human plasma clot. Intravenous infusion over 1 h in doses ranging between 0 and 0.50 mg/kg induced dose-dependent progressive clot lysis without systemic fibrinogen breakdown. The relative thrombolytic potencies, on a weight base, of the STA preparations versus Streptokinase were comparable in the platelet-poor clot model (50% lysis requiring 13 μg/kg STA and 12 μg/kg Streptokinase) and in the platelet-rich clot model (50% lysis with 28 μg/kg STA and with 32 μg/kg Streptokinase), but 5-fold higher in the platelet-enriched clot model (50% lysis with 46 μg/kg STA and with 210 μ/kg Streptokinase) and 2-fold higher in the mechanically compressed clot model (50% lysis with 36 μg/kg STA and with 71 μg/kg Streptokinase). Dog plasma at baseline contained Streptokinase-neutralising activity (neutralising 0.24±0.14 μg Streptokinase per ml plasma in a human plasma-based clot lysis assay, mean ±SD) but apparently no STA-neutralising activity. Repeated administration of 40 μg/kg over 1 h of Streptokinase at weekly intervals in 5 dogs, increased the Streptokinase-neutralising titre to 1.1±0.98 μg/ml plasma after 2 weeks and to 2.9±2.5 μg/ml after 3 weeks (p=0.13 and 0.05 versus baseline, respectively), whereas the thrombolytic potency towards a 125I-fibrin-labelled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 58±4% at baseline to 10±3% after 2 weeks and 4±1% after 3 weeks (p<0.001 vs baseline). Repeated weekly administration of an equipotent dose of STA (4 μg/kg) did not induce measurable STA-neutralising activity after 2 weeks and was associated with persistent, although somewhat reduced clot lysis (58 ± 4% lysis at baseline and 33±7% at 2 weeks, p=0.02). After 3 weeks however, STA-neutralising activity became detectable in plasma (0.34±0.30 μg/ml, p=0.07 vs baseline) and resistance to clot lysis became obvious (6±2% versus a baseline value of 58±4%, p<0.01). Thus, in the hamster model, STA has a thrombolytic potency towards platelet-poor and platelet-rich clots comparable to that of Streptokinase, but it is relatively more efficient than Streptokinase for the dissolution of platelet-enriched or retracted clots. Furthermore, STA might be less immunogenic than Streptokinase as evidenced by less rapid induction of antibody formation and resistance to clot lysis upon repeated administration. Thrombolytic therapy of patients with acute myocardial infarction with STA thus might constitute a potential alternative to treatment with Streptokinase, with a better efficacy towards platelet-rich arterial clots and possibly with reduced allergic side effects.
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comparative fibrinolytic properties of staphylokinase and Streptokinase in animal models of venous thrombosis
Thrombosis and Haemostasis, 1991Co-Authors: H. Roger Lijnen, J M Stassen, Kiyotaka Okada, Hideharu Fukao, Osamu Matsuo, I Vanlinthout, Desire CollenAbstract:: The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of Streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and Streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, Streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg Streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than Streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than Streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for Streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for Streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Guy L. Reed - One of the best experts on this subject based on the ideXlab platform.
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the mechanism of a bacterial plasminogen activator intermediate between Streptokinase and staphylokinase
Journal of Biological Chemistry, 2001Co-Authors: Irina Y Sazonova, Aiilyan K Houng, Brian R Robinson, Shakeel A. Chowdhry, Lizbeth Hedstrom, Guy L. ReedAbstract:Abstract The therapeutic properties of plasminogen activators are dictated by their mechanism of action. Unlike staphylokinase, a single domain protein, Streptokinase, a 3-domain (α, β, and γ) molecule, nonproteolytically activates human (h)-plasminogen and protects plasmin from inactivation by α2-antiplasmin. Because a Streptokinase-like mechanism was hypothesized to require the Streptokinase γ−domain, we examined the mechanism of action of a novel two-domain (α,β)Streptococcus uberis plasminogen activator (SUPA). Under conditions that quench trace plasmin, SUPA nonproteolytically generated an active site in bovine (b)-plasminogen. SUPA also competitively inhibited the inactivation of plasmin by α2-antiplasmin. Still, the lag phase in active site generation and plasminogen activation by SUPA was at least 5-fold longer than that of Streptokinase. Recombinant Streptokinase γ-domain bound to the b-plasminogen·SUPA complex and significantly reduced these lag phases. The SUPA-b·plasmin complex activated b-plasminogen with kinetic parameters comparable to those of Streptokinase for h-plasminogen. The SUPA-b·plasmin complex also activated h-plasminogen but with a lower k cat (25-fold) and k cat/K m (7.9-fold) than SK. We conclude that a γ-domain is not required for a Streptokinase-like activation of b-plasminogen. However, the Streptokinase γ-domain enhances the rates of active site formation in b-plasminogen and this enhancing effect may be required for efficient activation of plasminogen from other species.
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Identification of a plasminogen binding region in Streptokinase that is necessary for the creation of a functional Streptokinase-plasminogen activator complex.
Biochemistry, 1995Co-Authors: Guy L. Reed, ‡ Lee-fong Lin, Behnaz Parhami-seren, P. H. KussieAbstract:: Streptokinase is a plasminogen activator widely used to treat patients with myocardial infarction. However, Streptokinase is not a protease, and must first bind and interact with plasminogen to form an enzymatic complex. By measuring the binding of recombinant Streptokinase fragments to plasminogen, we have sought, first, to identify a plasminogen binding region in Streptokinase and, second, to explore the relation between binding (via this region) and the generation of a functional Streptokinase--plasminogen activator complex. Recombinant Streptokinase bound in a saturable and specific manner to human Glu-plasminogen with a dissociation constant of 4.2 x 10(-10) M. Recombinant Streptokinase fragments spanning amino acids 1-127 and 1-253 could not be shown to bind to Glu-plasminogen, whereas fragments spanning amino acids 1-352, 120-352, and 244-414 bound tightly to plasminogen and each fragment completely inhibited the binding of full-length Streptokinase to plasminogen. Although these latter Streptokinase fragments formed a complex with plasminogen, enzymatic assays indicated that none of them was capable of generating an active site. When the Streptokinase region shared by these three fragments, spanning residues 244-352, was expressed, it also bound plasminogen and competitively inhibited the formation of a functional plasminogen activator complex by full-length Streptokinase. Taken together, these data indicate that Streptokinase binds to plasminogen with high affinity, that a primary binding region for plasminogen is located within amino acids 244-352, and that binding via this region is necessary for the generation of a functional plasminogen activator complex.
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Mapping the antigenic regions of Streptokinase in humans before and after Streptokinase therapy.
Molecular Immunology, 1995Co-Authors: Behnaz Parhami-seren, M Lynch, Harvey D. White, Guy L. ReedAbstract:Streptokinase saves lives in patients suffering a myocardial infarction. However, because nearly all humans tested show antibodies against Streptokinase, allergic reactions to Streptokinase are common and may be severe. In this report we have analysed antibodies purified from normal blood donors and patients, before and after Streptokinase therapy, to identify antigenic regions of the Streptokinase molecule. Antibody to Streptokinase was seen in all subjects, but there were 20-30-fold differences between individuals in the antibody titer. These individual differences in titer persisted after SK treatment, though the titer for all patients rose an average of 7-fold 1 week after Streptokinase therapy. To identify the regions of Streptokinase to which the antibody bound, we employed a panel of well-characterized murine monoclonal antibodies and recombinant Streptokinase truncated fragments. Antibodies to three discrete regions of Streptokinase could be detected in all patients. Antibodies to two other regions, at the amino terminal and carboxyl terminus of the molecule, were found in many but not in all patients. However, antibodies to a sixth region of Streptokinase were uncommon and of very low titer. Interestingly, individuals receiving Streptokinase tended to show the same pattern of immunoreactivity after treatment as they had prior to Streptokinase. We conclude that although individual differences exist in the titers of Streptokinase antibody, certain regions of Streptokinase appear to be more antigenic or immunodominant.
V Aubert - One of the best experts on this subject based on the ideXlab platform.
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anaphylactoid purpura like vasculitis following fibrinolytic therapy role of the immune response to Streptokinase
Clinical and Experimental Rheumatology, 1994Co-Authors: J P Lantin, S Gattesco, A Duclos, Anne Zanchi, M D Schaller, A Pecoud, V AubertAbstract:We report the case of a patient who presented with a clinical picture of serum sickness with some characteristics of anaphylactoid purpura (Henoch-Schonlein purpura) five days after receiving Streptokinase as a treatment for myocardial infarction. The appearance of Henoch-Schonlein like vasculitis after Streptokinase treatment was particularly intriguing in view of the common association of streptococcus infection with this type of vasculitis. The production of Streptokinase specific IgG and IgA antibodies was studied in the patient and compared with six controls treated with identical doses of Streptokinase without adverse effects. A more rapid increase of Streptokinase specific IgA was detected in the patient, with a significant higher amount of Streptokinase specific IgA and IgG after six days of treatment. These results suggest that different kinetics could induce a precipitation of the immune complexes responsible for vasculitis. However, we cannot exclude that the IgA found in the vessel walls was only an "innocent bystander" deposited as a secondary event.
H. Roger Lijnen - One of the best experts on this subject based on the ideXlab platform.
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comparative thrombolytic and immunogenic properties of staphylokinase and Streptokinase
Fibrinolysis and Proteolysis, 1992Co-Authors: Desire Collen, I Vanlinthout, F De Cock, H. Roger Lijnen, Paul Declerck, J M StassenAbstract:The comparative thrombolytic properties of natural (STAN) and recombinant (STAR) staphylokinase (STA) and of Streptokinase were studied in hamsters with a pulmonary embolus consisting of a platelet-poor, platelet-rich (300000 platelets/μI), platelet-enriched (1500 000 platelets/ μl) or mechanically compressed human plasma clot. Intravenous infusion over 1 h in doses ranging between 0 and 0.50 mg/kg induced dose-dependent progressive clot lysis without systemic fibrinogen breakdown. The relative thrombolytic potencies, on a weight base, of the STA preparations versus Streptokinase were comparable in the platelet-poor clot model (50% lysis requiring 13 μg/kg STA and 12 μg/kg Streptokinase) and in the platelet-rich clot model (50% lysis with 28 μg/kg STA and with 32 μg/kg Streptokinase), but 5-fold higher in the platelet-enriched clot model (50% lysis with 46 μg/kg STA and with 210 μ/kg Streptokinase) and 2-fold higher in the mechanically compressed clot model (50% lysis with 36 μg/kg STA and with 71 μg/kg Streptokinase). Dog plasma at baseline contained Streptokinase-neutralising activity (neutralising 0.24±0.14 μg Streptokinase per ml plasma in a human plasma-based clot lysis assay, mean ±SD) but apparently no STA-neutralising activity. Repeated administration of 40 μg/kg over 1 h of Streptokinase at weekly intervals in 5 dogs, increased the Streptokinase-neutralising titre to 1.1±0.98 μg/ml plasma after 2 weeks and to 2.9±2.5 μg/ml after 3 weeks (p=0.13 and 0.05 versus baseline, respectively), whereas the thrombolytic potency towards a 125I-fibrin-labelled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 58±4% at baseline to 10±3% after 2 weeks and 4±1% after 3 weeks (p<0.001 vs baseline). Repeated weekly administration of an equipotent dose of STA (4 μg/kg) did not induce measurable STA-neutralising activity after 2 weeks and was associated with persistent, although somewhat reduced clot lysis (58 ± 4% lysis at baseline and 33±7% at 2 weeks, p=0.02). After 3 weeks however, STA-neutralising activity became detectable in plasma (0.34±0.30 μg/ml, p=0.07 vs baseline) and resistance to clot lysis became obvious (6±2% versus a baseline value of 58±4%, p<0.01). Thus, in the hamster model, STA has a thrombolytic potency towards platelet-poor and platelet-rich clots comparable to that of Streptokinase, but it is relatively more efficient than Streptokinase for the dissolution of platelet-enriched or retracted clots. Furthermore, STA might be less immunogenic than Streptokinase as evidenced by less rapid induction of antibody formation and resistance to clot lysis upon repeated administration. Thrombolytic therapy of patients with acute myocardial infarction with STA thus might constitute a potential alternative to treatment with Streptokinase, with a better efficacy towards platelet-rich arterial clots and possibly with reduced allergic side effects.
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comparative fibrinolytic properties of staphylokinase and Streptokinase in animal models of venous thrombosis
Thrombosis and Haemostasis, 1991Co-Authors: H. Roger Lijnen, J M Stassen, Kiyotaka Okada, Hideharu Fukao, Osamu Matsuo, I Vanlinthout, Desire CollenAbstract:: The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of Streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and Streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, Streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg Streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than Streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than Streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for Streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for Streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
